Bertha K. Madras, PhD Professor of Psychobiology Department of Psychiatry Harvard Medical School

Transcription

1 Bertha K. Madras, PhD Professor of Psychobiology Department of Psychiatry Harvard Medical School

2 Digitalis 1875 Atropine 1831 Aspirin 1853 Quinine 1820

3 Cocaine Cathinone Δ-9-tetrahydrocannabinol (THC) Methamphetamine Heroin

4 What are Designer Drugs? What Drives Designer Drug Markets? Trends? Are Designer Drugs Legal? Who Uses Bath Salts, Synthetic Cannabinoids, and Why? Effects and Harmful Effects? Summary

5 Bath salts: stimulants hallucinogens, entactogens, empathogens These are not bath salts!!!!!!! They are chemicals. Spice, K2 Cannabinoids: marijuana-like chemicals Dragonflys : Hallucinogens Morphine-like: Krokodil Tryptamines: Hallucinogens

6 Hallucinogens DOB Aleph-2 DOM 2C-D 2C-B 2CT-2 2-CE 2C-C 2C-I 2C-T-2 2C-T-4 2C-N 2C-P PIPERAZINES BZP MDBP mcpp TFMPP MeOPP DISSOCIATIVES Methoxetamine Ketamine Phencyclidine SYNTHETIC CANNABINOIDS CP 47,497 CP 55,940 Cannabicyclohexanol JWH-007, -018, -073, -081, -098, -122, -164, -210, UR-144 XLR-11 UR MDMA related PFA PFMA 6-APB MDAI 5-IAI MDAT CATHINONES Cathinone Methcathinone Mephedrone Flephedrone Pyrovalerone MDPV Pentylone Naphyrone HALLUCINOGENIC AMPHETAMINES (rigid dragonflies) 2C-Bfly Br-Fly Br-dragonfly TCB-2

7 Synthetic cannabinoids Synthetic cathinones Source: US DEA, Office of Division Control, National Forensic Laboratory Information System, 2012

8 NH 2 Phenethylamine ( PEA) NH 2 H N CH 3 O H N CH 3 CH 3 Amphetamine CH 3 Methamphetamine O CH 3 MDMA or ecstasy methylenedioxymethamphetamine H 3 C O CH 3 Cathinone O NH 2 N H 3 C O CH 3 Mephedrone O H N N CH 3 O Methylone Pyrovalerone Naphyrone MDPV or methylenedioxypyrovalerone O O O O O CH 3 H N N CH 3 ARE NOT Skin cleansers, perfumes or soothing lotions

9 If sold as Bath salts warning signs: Is it in a small packet? Is it labeled: not for human consumption? Is it labeled not illegal? Is it labeled adults only? If sold as plant food, fertilizer

10 H HO O N H O THC: phyto-cannabinoid made by plant Cannabis sativa JWH-018: synthetic cannabinoid made in chemistry laboratory O OH N Anandamide: endocannabinoid made by brain cells

11 NH 2 Phenethylamine ( PEA) O O NH 2 NH 2 Br Br H 3 C O 2C - Bfly O Br- D ragonfly

12 Desmorphine : Russian, response to tight heroin supply Synthesis: Simple with codeine, iodine, red phosphorus. Purity: Highly impure, contaminated with toxic, corrosive byproducts Psychoactive effects: Similar to heroin, shorter duration; brain damage Notoriety: produces severe tissue damage, phlebitis, gangrene Life expectancies: short

13 Dr. David Nichols Dr. John W Huffman Dr. Alexander Shulgin

14 New medications Basic science Publish research Publish patents

15 Red, yellow regions have high concentrations of CB1 cannabinoid receptor PET image CB1 MRI defines anatomy MRI, PET combined Terry et al., Quantitation of cannabinoid CB 1 receptors in healthy human brain using positron emission tomography and an inverse agonist radioligand. Neuroimage , 2009

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17 Internet: sales, production, information Deceptive Marketing Grey zone legal status Evade drug tests

18 To have novel feelings sensations experiences AND To share them Vivian Felsen

19 To evade drug testing Vivian Felsen

20 To evade legal issues Vivian Felsen

21 Marketed to teens and young adults Unknown composition of matter No consistency in manufacturing Not tested for human consumption Unknown actions in brain or body Unknown dosage, drug interactions

22 > 200 discussion forums, social media, online shops, websites (YouTube, ebay, Google, Google Insight) > 410 substances/products Information is valuable, as scientific data are scarce Spice, mephedrone, naphyrone, MDAI, MDPV were tracked from single source country to spread After made illegal, online searches decrease

23 12.00% 10.00% 8.00% 6.00% 4.00% 2.00% 0.00% 12th 10th 8th Spice, K2 "Bath salts" Synthetic marijuana 10 th, 12 th graders 2 nd most widely used drug after marijuana 8 th graders 3 rd most widely used drug after marijuana, inhalants Source: Monitoring the Future, Dec 2012

24 % Used synthetic cannabinoids Male Female Hetero LGBT No use Use No use Use Gender Orientation Alcohol use Marijuana use Adapted by CESAR from Stogner, J.M. and Miller, B.L., A Spicy Kind of High: A Profile of Synthetic Cannabinoid Users, Journal of Substance Use, Advance online publication (doi: / ), For more information, contact Dr. Stogner at stogner@ .unc.edu.

25 1. Actual or potential for abuse, addiction 2. Significant psychoactive effects 3. Risk to public health Driving under influence, suicides, homicides, drugs abused to evade drug screens, overdose illness, deaths 4. Analogs currently controlled, same reasons

26 October 2011: DEA controlled three synthetics, mephedrone, 3, 4-methylenedioxypyrovalerone (MDPV), and methylone, sold as bath salts plant food. March : DEA extended control of five fake marijuana products (JWH-018, JWH-073, JWH-200, CP- 47,497, cannabicyclohexanol. June 2012: 26 synthetic drugs, including 15 synthetic cannabinoids, placed under Controlled Substance Act. Possession, sale of these chemicals, or products that contain them, illegal in the United States.

27 New Jersey: bans six chemicals used to make designer drug 'bath salts' Investigation: Ban on Bath Salts, Designer Drugs is Working Dramatically Arkansas: State Health Officer Acts to Ban Designer Drug Nebraska b an on synthetic designer drugs advances Ohio: Senator Burke working to ban designer drugs. Florida: House Committee Passes Bill to Ban 27 Substances Used in Designer Drugs Michigan: Bills banning synthetic designer drugs headed to Gov. Snyder

28 Number of calls 20 0 Mar-12 Apr-12 May-12 Jun-12 Jul-12 Aug-12 Sep-12 Oct-12

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32 Brain Eyes, ears, nose, throat Lungs Heart, blood vessels Kidney, hormones Digestive tract Reproduction CB2 receptors Palpitations Shortness Of Breathe Chest Pain Dry Mouth Abdominal Pain Anorexia Vomiting Erectile Dysfunction Skin Discoloration Muscular Tension

33 Psychoactive effects: Aggression, dizziness, memory loss, seizures, blurred vision, anxiety, hallucinations, depression, dysphoria, euphoria, fatigue, increased energy and decreased concentration, panic and paranoia. Addiction: Mephedrone user survey; 50% considered it addictive, ~ 50% reported continuous use for > 48 h, and > 30% fulfilled 3+ criteria for abuse/addiction (DSM-IV). Addiction: Another survey (n=1,006); 17.5% of users reported addiction symptoms highest frequency of daily use falling in the year old age range.

34 Man repeatedly stabs himself in face University student runs head-on into traffic and killed Daughter attacks 71 year old mother with machete Mother leaves 2 year old on highway median and carries 5 year old Man runs into police station thinking someone hiding under his car Man jumps from 3 rd story window fleeing from non-existent person Couple destroy home walls trying to stab imaginary people Man flees car he thinks is melting and chased by electricity 19 year old man arrested pointing 3 rifles at family members Woman driving with toddler arrested after banging head on steering wheel Man arrested for disorderly conduct eats dirt while handcuffed Man rams stolen car into front door of store and steals bath salts Man arrested at grocery store after damage and drinking hand sanitizer Man makes 911 call being chased by people with rifles

35 Organ system Cardiovascular Psychological Neurological Musculoskeletal Gastrointestinal Pulmonary Ears, nose, throat Effects Palpitations, tachycardia, chest pain, vasoconstriction, myocardial infarct. Aggression, anger, anxiety, agitation, auditory visual hallucinations, depression, dysphoria, empathy, euphoria, fatigue Seizures, tremor, dizziness, memopry loss, cerebral edema, headaches, lightheaded Arthralgia, coldness, numbness, discoloration, numbness, tingling of limbs, musclar tension, cramping Abdominal pain, anorexia, nausea, vomiting Shortness of breathe Dry mouth, nasal pain, tinnitus

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37 Bath salt drug Transporter Brain message

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39 Cathinones do not all confer same effects or health risks. They engender risks and adverse consequences: (a) emergency department mentions (b) persistence of effects after 24 hours (c) addictive potential (d) psychiatric, cardiovascular effects (e) deaths

40 Bliss Black Mamba Blaze Bombay Blue Genie Spice JWH -018 JWH -073, -250 herbal smoking mixture incense herbal blends air freshener not for human consumption.

41 Source: DEA

42 What: Synthetic forms of marijuana What: Mixture of dried, shredded plants sprayed with THC-like chemicals; THC is the most active constituent of marijuana. Strong clove smell Onset time: 5-15 minutes (smoked) Duration: 1-8+ hours Effects: Many Comparison with marijuana: effects may be extreme of smoked marijuana or different.

43 Cannabis ~= Synthetic Cannabinoids High heart rate Red eyes Anxiety Mild sedation Hallucinations Acute psychosis Memory deficits Symptoms More Typical of Synthetics Seizures Low blood potassium High blood pressure Nausea/vomiting Agitation Violent behavior Coma SOURCES: Hermanns-Clausen et al. (In Press), Addiction; Rosenbaum et al. (2012). Journal of Medical Toxicology; Forrester et al. (2011). Journal of Addictive Disease; Schneir et al. (2011). Journal of Emergency Medicine.

44 Positive Psychoactive Effects Pleasant Euphoria Relaxation Sedation Negative Psychoactive Effects Severe paranoia, endangering self, others Agitation, delirium Headaches Anxiety, panic attacks Loss of control Confusion, hallucinations, psychosis Suicidal thoughts Seizures, tremors Impaired short-term memory concentration Persistent psychosis

45 Brain Eyes, ears, nose, throat Lungs Heart, blood vessels Kidney, hormones Digestive tract Reproduction Vomiting, nausea Eye soreness CB2 receptors Profuse sweating Severe GI symptoms Muscle spasms Increased blood pressure, heart rate Chest Pain Serious injury or death

46 Abusers in ER seek treatment for addiction Multiple deaths associated with these alone or combined Organ system Effects Psychological Neurological Cardiovascular Metabolic Gastrointestinal Autonomic, other Anxiety, aggression, agitation, confusions, dysphoria, paranoia, irritation, panic attack, hallucinations Seizures, loss of consciousness Tachycardia, hypertension, chest pain, cardiac ischemia Hypokalemia, hyperglycemia Nausea, vomiting Fever, mydriasis conjunctivitis,

47 CDC: Multiple States, 2012 MMWR Weekly February 15, 2013 / 62(06);93-98

48 Marijuana plant makes ~ 80 phytocannabinoids THC =#1 Brain, other organs make Endocannabinoids Anandamide: arachidonoylethanolamide 2-AG: 2-arachidonoylglycerol 7 or more made in brain and in other tissues O H OH N OH ANANDAMIDE O O C O OH OH Synthetic cannabinoids: 1,000s made by chemists Δ9-THC (Gaoni & Mechoulam, 1964) 2-ARACHIDONOYL GLYCEROL (2-AG)

49 Endocannabinoid made by the brain THC made by the plant, Cannabis Sativa

50 Modulates brain communication by reducing chemical messages Critical for brain development Controls chemical messages critical for pleasure, mood, pain, appetite, motivation, memory THC, synthetics affect anandamide control of brain signals THC, synthetics effects are prolonged, more powerful, different

51 Addiction to JWH-018, JWH-200, JWH-073, CP- 47,497, cannabicyclohexanol: physiological and psychological dependence liability similar to that of marijuana and THC. Physical and psychological withdrawal: elevated blood pressure, restlessness, drug craving, nightmares, sweating, nausea, tremor and headache, palpitation, insomnia, headache, diarrhea, vomiting.

52 Spice and K2, widely used by high school and college students, are emerging public health challenges. Their rapid rise in popularity, ready access from multiple sources production of acute psychological distress toxicity potentially long term harmful effects ability to evade standard drug tests, require a massive public education campaign and strategies for deterrence in healthcare systems are needed to respond to this emerging threat.

53 1. Phenethylamines : similar to mescaline 2. Dragonfly: 2C-Bfly, Br-fly, Br-dragonfly) 3. SalvinorinA: 5.9% among 12 th graders 4. Smiles: 5. Dissociative anesthetics: methoxetamine, ketamine, PCP 6. DMAA (1,3-dimethylamylamine): party pills, weight loss, sports performance supplements.

54 Smiles or "25-I : analog of 2C-B: drug is the newest of "research chemicals" available for purchase online. 25-I's chemical makeup varies from batch to batch, effects similar to LSD, 2C-I, and 2C-B, all banned under federal law. Psychoactive effects: hallucinations, in some cases severe brain hemorrhaging, death. Trend in Connecticut: among high school and college students. Public awareness: Unaware of potentially fatal side effects.

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57 2Cs are designer drugs emerging as new drugs of abuse. The published literature concerning 2Cs is limited; a few 2Cs have been studied, i.e., 2C-T-7, 2C-B, and 2C-E, limited information. A syndrome consistent with excited delirium including severe agitation, aggression, violence, seizures, and hyperthermia is consistently depicted in lethal 2C cases. No antidotes for 2C intoxication. Treatment is limited to supportive care but should include rapid sedation, aggressive treatment of severe hyperthermia and excited delirium.

58 Methoxamine 2011 Dissociative, pain suppression Sold as ketamine derivative Similar to PCP 5-7 hour duration Deaths Methylhexanamine Stimulant Dietary supplement market Cathinone replacement DMAA FDA challenges for safety evidence Deaths

59 Roth et al, PLoS One. 2013;8(3):e doi: /journal.pone Epub 2013 Mar 19.

60 A vast array of new drugs are being introduced Contents, doses of substances unknown Drug interactions unknown Short-, long-term effects unknown Toxicity reports are increasing rapidly Effects on developing brain unknown Routine drug testing currently not feasible Legal status for many uncertain

61 Impact on brain function, behavior, organ systems, is unacceptably high Preclinical research on each drug (100 s) is not feasible unless massive scale-up of research funding Drug combinations challenge research We are engaged in a massive human experiment, which will require years to resolve

62 Avoid consuming drugs that affect thinking, feelings, judgment. The adolescent brain is fragile as it is not fully formed. No one knows what a street drug contains, how much, impurities, toxins. Intoxication is risky, for health, for making unsafe or unhealthy choices. Any drug, legal or not, if not prescribed / used for medical purposes, can be unsafe. No one knows long term effects of designer drugs.

63 Pleasure Full, legal access Pain Medical, social, economic, legal, costs

64 1 = no added risk (adapted from: Callaghan RC, Cunningham JK, Verdichevski M, Sykes, J, Jaffer SR, Kish SJ. (2012) All-cause mortality among individuals with disorders related to the use of methamphetamine: A comparative cohort study. Drug Alcohol Depend. doi: /j.drugalcdep )